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Background & aimsGene expression patterns of CD8+ T cells have been reported to correlate with clinical outcomes of adults with inflammatory bowel diseases (IBD). We aimed to validate these findings in independent patient cohorts.MethodsWe obtained peripheral blood samples from 112 children with a new diagnosis of IBD (71 with Crohn's disease and 41 with ulcerative colitis) and 19 children without IBD (controls) and recorded medical information on disease activity and outcomes. CD8+ T cells were isolated from blood samples by magnetic bead sorting at the point of diagnosis and during the course of disease. Genome-wide transcription (n = 192) and DNA methylation (n = 66) profiles were generated using Affymetrix and Illumina arrays, respectively. Publicly available transcriptomes and DNA methylomes of CD8+ T cells from 3 adult patient cohorts with and without IBD were included in data analyses.ResultsPreviously reported CD8+ T-cell prognostic expression and exhaustion signatures were only found in the original adult IBD patient cohort. These signatures could not be detected in either a pediatric or a second adult IBD cohort. In contrast, an association between CD8+ T-cell gene expression with age and sex was detected across all 3 cohorts. CD8+ gene transcription was clearly associated with IBD in the 2 cohorts that included non-IBD controls. Lastly, DNA methylation profiles of CD8+ T cells from children with Crohn's disease correlated with age but not with disease outcome.ConclusionsWe were unable to validate previously reported findings of an association between CD8+ T-cell gene transcription and disease outcome in IBD. Our findings reveal the challenges of developing prognostic biomarkers for patients with IBD and the importance of their validation in large, independent cohorts before clinical application.

Original publication




Journal article



Publication Date





232 - 244.e7


Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom; Department of Paediatric Gastroenterology, Hepatology and Nutrition, Cambridge University Hospitals, Addenbrooke's, Cambridge, United Kingdom.


CD8-Positive T-Lymphocytes, Humans, Inflammatory Bowel Diseases, Prognosis, Case-Control Studies, Predictive Value of Tests, Age Factors, DNA Methylation, Transcription, Genetic, Adolescent, Adult, Child, Child, Preschool, Female, Male, Young Adult